A preliminary study on the effects of fecal microbiota transplantation on the intestinal microecology of patients with severe pneumonia during the convalescence period / 中华危重病急救医学

OBJECTIVE@#To investigate the effects of fecal microbiota transplantation (FMT) on intestinal microbiome and organism in patients with severe pneumonia during the convalescence period.@*METHODS@#A prospective non-randomized controlled study was conducted. From December 2021 to May 2022, patients with severe pneumonia during the convalescence period who received FMT (FMT group) and patients with severe pneumonia during the convalescence period who did not receive FMT (non-FMT group) admitted to the First Affiliated Hospital of Guangzhou Medical University were enrolled. The differences of clinical indicators, gastrointestinal function and fecal traits between the two groups were compared 1 day before and 10 days after enrollment. The 16S rDNA gene sequencing technology was used to analyze the changes of intestinal flora diversity and different species in patients with FMT before and after enrollment, and metabolic pathways were analyzed and predicted by Kyoto Encyclopedia of Genes and Genomes database (KEGG). Pearson correlation method was used to analyze the correlation between intestinal flora and clinical indicators in FMT group.@*RESULTS@#The level of triacylglycerol (TG) in FMT group was significantly decreased at 10 days after enrollment compared with before enrollment [mmol/L: 0.94 (0.71, 1.40) vs. 1.47 (0.78, 1.86), P < 0.05]. The level of high-density lipoprotein cholesterol (HDL-C) in non-FMT group was significantly decreased at 10 days after enrollment compared with before enrollment (mmol/L: 0.68±0.27 vs. 0.80±0.31, P < 0.05). There were no significant differences in other clinical indexes, gastrointestinal function or fecal character scores between the two groups. Diversity analysis showed that the α diversity indexes of intestinal flora in FMT group at 10 days after enrollment were significantly higher than those in non-FMT group, and β diversity was also significantly different from that in non-FMT group. Differential species analysis showed that the relative abundance of Proteobacteria at the level of intestinal flora in FMT group at 10 days after enrollment was significantly lower than that in non-FMT group [8.554% (5.977%, 12.159%) vs. 19.285% (8.054%, 33.207%), P < 0.05], while the relative abundance of Fusobacteria was significantly higher than that in non-FMT group [6.801% (1.373%, 20.586%) vs. 0.003% (0%, 9.324%), P < 0.05], and the relative abundance of Butyricimonas, Fusobacterium and Bifidobacterium at the genus level of the intestinal flora was significantly higher than that in non-FMT group [Butyricimonas: 1.634% (0.813%, 2.387%) vs. 0% (0%, 0.061%), Fusobacterium: 6.801% (1.373%, 20.586%) vs. 0.002% (0%, 9.324%), Bifidobacterium: 0.037% (0%, 0.153%) vs. 0% (0%, 0%), all P < 0.05]. KEGG metabolic pathway analysis showed that the intestinal flora of FMT group was changed in bisphenol degradation, mineral absorption, phosphonate and phosphinate metabolism, cardiac muscle contraction, Parkinson disease and other metabolic pathways and diseases. Correlation analysis showed that Actinobacteria and prealbumin (PA) in intestinal flora of FMT group were significantly positively correlated (r = 0.53, P = 0.043), Bacteroidetes was positively correlated with blood urea nitrogen (BUN; r = 0.56, P = 0.029) and complement C3 (r = 0.57, P = 0.027), Firmicutes was positively correlated with BUN (r = 0.56, P = 0.029) and complement C3 (r = 0.57, P = 0.027), Fusobacteria was significantly positively correlated with immunoglobulin M (IgM; r = 0.71, P = 0.003), Proteobacteria was significantly positively correlated with procalcitonin (PCT; r = 0.63, P = 0.012) and complement C4 (r = 0.56, P = 0.030).@*CONCLUSIONS@#FMT can reduce TG level, reconstruct intestinal microecological structure, change body metabolism and function, and alleviate inflammatory response by reducing the relative abundance of harmful bacteria in patients with severe pneumonia during the convalescence period.

Preliminary study on the effect of fecal microbiota transplantation on neurobehavior and gut microbiota of offspring rats exposed to arsenic / 中华劳动卫生职业病杂志

Objective: To explore the effects of fecal microbiota transplantation (FMT) on neurobehavior and gut microbiota of arsenic-exposed offspring rats. Methods: In April 2021, Thirty-six SPF SD rats aged 8 weeks were seleted, rats were ranked by weight and divided into four groups according to randomized block design, namely control group, arsenic exposure group (As group) , arsenic+normal saline group (As+NaCl group) and As+FMT group, 6 females and 3 males in each group. Fecal microbiota fluid were provided by feces of rats in control group. Rats drank tap water containing 75 mg/L sodium arsenite for one week and then were caged together. The arsenic exposure was terminated until the pups were born. Female rats with vaginal plug were treated with fecal microbiota fluid via gavage during neurodevelopmental teratogenic window period. The volume of gavage was 1 ml/100 g with once every two days, for a total of three times. Weight alterations of offspring rats were recorded every week after weaning, and when offspring rats grew up for 6 weeks, Morris test and open field experiment was used to observe learning and memory abilities, as well as neurobehavioral performance of autonomous exploration and tension, respectively. 16S rDNA sequencing technology was used to detect microbiota diversities in fecal samples of rats in As group and As+FMT group. Results: Compared with the control group, the ratio of swimming distance and staying time in the target quadrant and the times of crossing the platform of rats in As group decreased significantly, and the motor distance, times entering central zone and the number of grid crossing of rats decreased significantly (P<0.05) . Compared with As group, the ratio of swimming distance in target quadrant, the motor distance in central zone and times entering central zone of rats in As+FMT group were evidently increased (P<0.05) . The analysis of fecal microbiota diversities showed that, at the phyla level, the relative abundance of Bacteroidetes in feces of rats in As+FMT group was higher than that in As group (68.34% vs 60.55%) , while the relative abundance of Firmicutes was lower than that in As group (28.02% vs 33.48%) . At the genus level, the relative abundance of Prevotella in As+FMT group was significantly higher than that in As group, becoming the dominant genus (42.08% vs 21.78%) . Additionally, compared with As group, a total of 22 genus were increased with 21 decreased genus in As+FMT group (P<0.05) . LEfSe analysis showed that dominant genuses in As+FMT group were Prevotella and UCG_005, and their relative abundance was significantly higher than that of As group (P<0.05) . Conclusion: FMT may alleviate the impaired learning and memory ability and anxiety like behavior of the offspring rats exposed to arsenic, and improve the disrupted gut microbiota.

Clinical study of 19 cases of steroid-refractory gastrointestinal acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation with fecal microbiota transplantation / 中华血液学杂志

Objective: To investigate the clinical efficacy of fecal microbiota transplantation (FMT) for treating steroid-refractory gastrointestinal acute graft-versus-host disease (GI-aGVHD) . Methods: This analysis included 29 patients with hematology who developed steroid-refractory GI-aGVHD after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Huaian Hospital Affiliated to Xuzhou Medical University from March 2017 to March 2022. Among them, 19 patients underwent FMT treatment (the FMT group) and 10 patients did not (the control group). The efficacy and safety of FMT were assessed, as well as the changes in intestinal microbiota abundance, lymphocyte subpopulation ratio, peripheral blood inflammatory cytokines, and GVHD biomarkers before and after FMT treatment. Results: ① Complete remission of clinical symptoms after FMT was achieved by 13 (68.4%) patients and 2 (20.0%) controls, with a statistically significant difference (P<0.05). Intestinal microbiota diversity increased and gradually recovered to normal levels after FMT and FMT-related infections did not occur. ②The proportion of CD3(+) and CD8(+) cells in the FMT group after treatment decreased compared with the control group, and the ratio of CD4(+), regulatory T cells (Treg), and CD4(+)/CD8(+) cells increased (all P< 0.05). The interleukin (IL) -6 concentration in the FMT group was lower than that in the control group [4.15 (1.91-5.71) ng/L vs 6.82 (2.40-8.91) ng/L, P=0.040], and the IL-10 concentration in the FMT group was higher than that in the control group [12.11 (5.69-20.36) ng/L vs 7.51 (4.10-9.58) ng/L, P=0.024]. Islet-derived protein 3α (REG3α) was significantly increased in patients with GI-aGVHD, and the REG3α level in the FMT group was lower than that in the control group after treatment [30.70 (10.50-105.00) μg/L vs 74.35 (33.50-139.50) μg/L, P=0.021]. Conclusion: FMT is a safe and effective method for the treatment of steroid-refractory GI-aGVHD by restoring intestinal microbiota diversity, regulating inflammatory cytokines, and upregulating Treg cells.

Interaction between mucus layer and gut microbiota in non-alcoholic fatty liver disease: Soil and seeds / 中华医学杂志(英文版)

The intestinal mucus layer is a barrier that separates intestinal contents and epithelial cells, as well as acts as the "mucus layer-soil" for intestinal flora adhesion and colonization. Its structural and functional integrity is crucial to human health. Intestinal mucus is regulated by factors such as diet, living habits, hormones, neurotransmitters, cytokines, and intestinal flora. The mucus layer's thickness, viscosity, porosity, growth rate, and glycosylation status affect the structure of the gut flora colonized on it. The interaction between "mucus layer-soil" and "gut bacteria-seed" is an important factor leading to the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Probiotics, prebiotics, fecal microbiota transplantation (FMT), and wash microbial transplantation are efficient methods for managing NAFLD, but their long-term efficacy is poor. FMT is focused on achieving the goal of treating diseases by enhancing the "gut bacteria-seed". However, a lack of effective repair and management of the "mucus layer-soil" may be a reason why "seeds" cannot be well colonized and grow in the host gut, as the thinning and destruction of the "mucus layer-soil" is an early symptom of NAFLD. This review summarizes the existing correlation between intestinal mucus and gut microbiota, as well as the pathogenesis of NAFLD, and proposes a new perspective that "mucus layer-soil" restoration combined with "gut bacteria-seed" FMT may be one of the most effective future strategies for enhancing the long-term efficacy of NAFLD treatment.

Trasplante de microbiota fecal por colonoscopía en paciente mayor de 65 años con infección recurrente de Clostridioides difficile: aún una estrategia subutilizada / Fecal microbiota transplantation in an older patient with Clostridioides difficile recurrent infection. Report of one case

Clostridioides difficile infection (CDI) is a major public health problem and responsible for significant morbidity and mortality. Eighty percent of CDIs occur in adults older than 65 years of age due to a decreased gastrointestinal microbial diversity, immunosenescence and frailty. Thus, the most reported risk factor for recurrent CDI is older age since nearly 60% of cases occur in individuals aged ≥ 65 years. Fecal microbiota transplantation (FMT) is a highly cost-effective alternative to antibiotic treatment for patients with recurrent CDI. We report a 75-year-old male with recurrent CDI, who received a FMT after several unsuccessful antimicrobial treatments. He had a satisfactory evolution after the procedure and remained without diarrhea during the ensuing five months.

Experience of a gastroenterology center in fecal microbiota transplantation in the treatment of Clostridioides Difficile / Experiência de um centro de gastroenterologia em transplante de microbiota fecal no tratamento de Clostridioides difficile

Background: The treatment of Clostridioides difficile is based on an antibiotics cycle, but for individuals who have more than two recurrences, fecal microbiota transplantation can be considered as a therapeutic option. Objective: To describe the technique and results of fecal microbiota transplantation performed for recurrent infection by Clostridioides difficile. Methods: Retrospective, cross-sectional study based on a review of medical records of patients undergoing transplantation of fecal microbiota. Data were obtained on the criteria used to select the donor, the preparation of stools in the laboratory and the method of delivery of the material offered, as well as information regarding the characteristics of the recipient, such as: gender, age, comorbidities, hospitalizations, use of antibiotics prior to infection, clinical presentation, diagnosis and treatments performed for Clostridioides difficile. After transplantation, data on efficacy, outcome, follow-up time and procedure complications were considered. Results: Between 2012 and 2019, 11 patients underwent fecal microbiota transplantation. The use of antibiotics prior to infection occurred in 9 patients, no patient was hospitalized in the previous 6 months due to another etiology. All had at least 2 cycles of vancomycin for recurrent disease. Of the total of 11 patients, 2 required 2 infusions and 1 patient required 3, totaling 15 fecal microbiota transplants. The success rate was 81.8% with only one infusion and 90.9% resolution considering patients who needed more than one infusion. Conclusion: Fecal microbiota transplantation is a feasible therapy with resolution in 90.9% of cases as a treatment for recurrent Clostridioides difficile infection.

Contexto: O tratamento do Clostridioides difficile é baseado em ciclo antimicrobiano, mas para os indivíduos que apresentam mais de duas recorrências, pode-se considerar o transplante de microbiota fecal como opção terapêutica. Objetivo: Descrever a técnica e os resultados do transplante de microbiota fecal realizados para infecção recorrente por Clostridioides difficile. Métodos: Estudo retrospectivo, transversal, baseado em revisão de prontuários de pacientes submetidos ao transplante de microbiota fecal. Foram obtidos dados sobre os critérios empregados para seleção do doador, o preparo das fezes e o método de entrega do material, além de informações referentes às características do receptor, como: sexo, idade, comorbidades, internamentos, uso de antimicrobiano prévio à infecção, apresentação clínica, diagnóstico e tratamentos realizados para o Clostridioides difficile. Após o transplante, dados sobre eficácia, desfecho, tempo de seguimento e complicações do procedimento foram considerados. Resultados: Entre 2012 e 2019, 11 pacientes foram submetidos ao transplante de microbiota fecal. O uso de antimicrobiano prévio à infecção ocorreu em 9 pacientes, nenhum paciente internou nos 6 meses anteriores por outra etiologia. Todos fizeram pelo menos 2 ciclos de vancomicina para doença recorrente. Do total de 11 pacientes, 2 necessitaram de 2 infusões e 1 paciente necessitou de 3, totalizando 15 transplantes de microbiota fecal. O sucesso foi de 81,8% com apenas uma infusão e resolução de 90,9% considerando pacientes que necessitaram de mais de uma infusão. Conclusão: O transplante de microbiota fecal é uma terapia factível e com resolução em 90,9% dos casos como tratamento de infecção recorrente por Clostridioides difficile.

Fecal transplantation can alleviate tic severity in a Tourette syndrome mouse model by modulating intestinal flora and promoting serotonin secretion / 中华医学杂志(英文版)

BACKGROUND@#: Tourette syndrome (TS) is a neuropsychiatric disorder with onset in childhood that warrants effective therapies. Gut microbiota can affect central physiology and function via the microbiota-gut-brain axis. Therefore, the gut microbiota plays an important role in some mental illnesses. A small clinical trial showed that fecal microbiota transplantation (FMT) may alleviate TS symptoms in children. Herein, FMT effects and mechanisms were explored in a TS mouse model.@*METHODS@#: TS mice model (TSMO) (n = 80) were established with 3,3'-iminodipropionitrile, and 80 mice were used as controls. Mice were grouped into eight groups and were subjected to FMT with feces from children or mice with or without TS, or were given probiotics. Fecal specimens were collected 3 weeks after FMT. 16S rRNA sequencing, behavioral observation, and serum serotonin (5-HT) assay were performed. Differences between groups were analyzed using Mann-Whitney U test and Kolmogorov-Smirnov (KS) tests.@*RESULTS@#: A total of 18 discriminative microbial signatures (linear discriminant analysis score > 3) that varied significantly between TS and healthy mice (CONH) were identified. A significant increase in Turicibacteraceae and Ruminococcaceae in TSMO after FMT was observed (P  < 0.05). Compared with non-transplanted TSMO, the symptoms of those transplanted with feces from CONH were alleviated (W = 336, P = 0.046). In the probiotic and FMT experiments, the serum 5-HT levels significantly increased in TSMO that received probiotics (KS = 1.423, P = 0.035) and in those transplanted with feces from CONH (W = 336.5, P = 0.046) compared with TSMO without transplantation.@*CONCLUSIONS@#: This study suggests that FMT may ameliorate TS by promoting 5-HT secretion, and it provides new insights into the underlying mechanisms of FMT as a treatment for TS.

The Effect of Stool Transplantation on Weight Control in Obese Rats / O efeito do transplante de fezes no controle de peso em ratos obesos

Abstract Introduction Obesity is defined as a multifactorial metabolic syndrome in which there is an excessive number of fat cells within the tissues. It is discussed that intestinal microbiota might have a relevant relation with obesity, since it is relevantly altered in obese patients. Objectives To assess the effect of stool transplantation (ST) in the condition of obesity and its outcomes in an experimental model of cafeteria diet by analyzing histology and weight gain. Methods Forty male Wistar rats were randomly assigned to 5 groups: control (CO), control with antibiotics (CO+ATB), obesity (CAF+ATB), stool transplantation (ATB+ ST) and obesity with stool transplantation (CAF+ATB+ST). During the experiment, obesity induction groups received cafeteria diet, whereas the remaining groups had normal diet ad libitum. After 3 months, daily ST was carried out for 8 weeks by gavage procedure. The animals were euthanized, and the small intestine was harvested for further analysis. Results It was observed that before starting the ST, the cafeteria and normal diet groups had significant weight difference (p<0,0001). In the comparison between CAF+ATB and CAF+ATB+ST during the gavage period, the CAF+ATB+ST group presented lower weight gain (p=0.0017). The histopathological evaluation show that the ATB+ST group did not present intestinal crypt distortion. Conclusion Cafeteria diet resulted in an expected weight gain. In relation to the ST, it has been shown that the procedure is effective in reducing weekly weight gain. Apparently, there was no induction of disabsortive syndrome in nonobese animals that received ST.

Resumo Introdução A obesidade é definida como uma síndrome metabólica multifatorial, na qual existe um número excessivo de células de gordura nos tecidos. Discute-se que a microbiota intestinal pode estar relacionada com a obesidade, uma vez que ela é alterada de forma relevante em pacientes obesos. Objetivos Avaliar o efeito do transplante de fezes (TF) na obesidade induzida por um modelo experimental de dieta de cafeteria. Métodos Quarenta ratos Wistar foram distribuídos aleatoriamente em 5 grupos: controle (CO), controle com antibióticos (CO+ATB), obesidade (CAF+ATB), transplante de fezes (ATB+TF) e obesidade com transplante de fezes (CAF+ATB+TF). Durante o experimento, os grupos de indução de obesidade receberam dieta de cafeteria, enquanto os demais grupos tiveram dieta ad libitum normal. Após 3 meses, o TF diário foi realizado por 8 semanas por meio de gavagem intragástrica. Os animais foram sacrificados e o intestino delgado foi colhido para análise posterior. Resultados Observou-se que antes de iniciar o TF, os grupos de dieta de cafeteria e dieta normocalórica apresentavam diferença significativa de peso (p<0,0001). Ao comparar os grupos CAF+ATB e CAF+ATB+TF durante o período de gavagem, o grupo CAF+ATB+TF apresentou menor ganho de peso (p=0,0017). A avaliação histopatológica mostra que nenhum dos animais do grupo TF+ATB apresentou distorções nas criptas intestinais. Conclusão A dieta da cafeteria resultou em um ganho de peso esperado. Em relação ao TF, demonstrou-se que o procedimento é eficaz na redução do ganho de peso semanal. Aparentemente, não houve indução da síndrome disabsortiva em animais não obesos que receberam TF.

Advances in fecal microbiota transplantation for treatment of Parkinson's disease / 生物工程学报

Parkinson's disease (PD) is a common neurodegenerative disease in middle-aged and elderly people. Patients with PD often suffer from gastrointestinal symptoms in the early stage of the disease. Several studies have confirmed that gut microbiota is involved in the progress of PD. As one of the most effective ways to reconstruct the gut microbiota, fecal microbiota transplantation (FMT) has shown potential therapeutic effects on PD. This review summarizes the basic and clinical studies of FMT in the treatment of PD.

Microbe-based management for colorectal cancer / 中华医学杂志(英文版)

Colorectal cancer (CRC) is one of the most prevalent, most lethal cancers in the world. Increasing evidence suggests that the intestinal microbiota is closely related to the pathogenesis and prognosis of CRC. The normal microbiota plays an essential role in maintaining gut barrier function and the immune microenvironment. Recent studies have identified carcinogenic bacteria such as enterotoxigenic Bacteroides fragilis (ETBF) and Streptococcus gallolyticus (S. gallolyticus), as well as protective bacterial such as Akkermansia muciniphila (A. muciniphila), as potential targets of CRC treatment. Gut microbiota modulation aims to restore gut dysbiosis, regulate the intestinal immune system and prevent from pathogen invasion, all of which are beneficial for CRC prevention and prognosis. The utility of probiotics, prebiotics, postbiotics, fecal microbiota transplantation and dietary inventions to treat CRC makes them novel microbe-based management tools. In this review, we describe the mechanisms involved in bacteria-derived colorectal carcinogenesis and summarized novel bacteria-related therapies for CRC. In summary, we hope to facilitate clinical applications of intestinal bacteria for preventing and treating CRC.

Trasplante de microbiota fecal en la infección por Clostridioides difficile / Faecal microbiota transplantation for Clostridioides difficile infection

Resumen La infección por Clostridioides difficile (iCD) es la causa más frecuente de diarrea nosocomial. La primera línea terapéutica es la vancomicina asociada o no al metronidazol. En los últimos años se incrementó el número de fracasos terapéuticos con una mayor frecuencia de formas refractarias o recurrentes. El trasplante de microbiota fecal (TMF) ha surgido como una opción terapéutica para estos casos. Se evaluó la seguridad y la tasa de resolución empleando el TMF en un estudio observacional abierto y prospectivo de 21 pacientes con iCD recurrentes o refractarias internados entre los años 2016 y 2019. La edad media fue de 76.5 años (33-92). Diez presentaron una forma recurrente y 11 una refractaria, 18 fueron graves y 3 fulminantes. En 20 casos el TMF se administró por la vía digestiva alta y en uno por presentar íleo se utilizó la vía baja. Se empleó TMF de heces frescas en un caso y el resto recibió muestras congeladas de un banco de microbiota. Veinte pacientes (95.2%) tuvieron respuesta terapéutica favorable sin presentar recurrencias. Un caso recurrente, con osteomielitis y falla multiorgánica, no tuvo resolución tras dos TMF. La respuesta fue similar en las formas recurrentes y refractarias. Siete pacientes (31%) tuvieron efectos adversos leves y autolimitados. El TMF ha demostrado una alta eficacia como tratamiento de rescate de las formas graves de iCD, con escasos y leves efectos adversos. Contar con un banco de microbiota fecal resulta fundamental para disponer de este recurso terapéutico oportunamente.

Abstract Clostridiodes difficile infection (CDi) is the most common cause of nosocomial diarrhea. Vancomycin, associated or not to metronidazol, is the treatment of choice. However, the rate of treatment failure has increased over the last years and fecal microbiota transplantation (FMT) has emerged as a therapeutic option. To evaluate safety and efficacy of FMT were enrolled 21 hospitalized patients with refractory or recurrent CDi between 2016 and 2019. Fourteen (66%) patients were men and the average age was 76.5 years (range 33-92). Ten had recurrent and 11 refractory CDi, and 18 presented severe and 3 fulminant clinical forms. In 20 cases the FMT was delivered through a nasojejunal tube and in one patient with ileo via enema infusion. Frozen fecal from a stool bank were administered in 20 and in the remaining was used fresh fecal matter. The rate of resolution was observed in 20 patients (95.2%) and none presented recurrence. The response rate was similar in recurrent or refractory forms (9/10 vs 11/11 respectively). One patient with osteomyelitis and multiple organ failure received 2 FMT without response and died. Seven patients (31%) presented mild and self-limited adverse effects. FMT has shown a high efficacy as rescue treatment in cases with refractory or recurrent CDi regardless of severity, with mild side effects. Availability of a stool banks provide reliable, timely and equitable access to FMT for CDi.

Estruturação de centro de transplante de microbiota fecal em hospital universitário no Brasil / Structuring a fecal microbiota transplantation center in a university hospital in brazil

ABSTRACT BACKGROUND: Fecal microbiota transplantation (FMT) is an important therapeutic option for recurrent or refractory Clostridioides difficile infection, being a safe and effective method. Initial results suggest that FMT also plays an important role in other conditions whose pathogenesis involves alteration of the intestinal microbiota. However, its systematized use is not widespread, especially in Brazil. In the last decade, multiple reports and several cases emerged using different protocols for FMT, without standardization of methods and with variable response rates. In Brazil, few isolated cases of FMT have been reported without the implantation of a Fecal Microbiota Transplantation Center (FMTC). OBJECTIVE: The main objective of this study is to describe the process of implanting a FMTC with a stool bank, in a Brazilian university hospital for treatment of recurrent and refractory C. difficile infection. METHODS: The center was structured within the criteria required by international organizations such as the Food and Drug Administration, the European Fecal Microbiota Transplant Group and in line with national epidemiological and regulatory aspects. RESULTS: A whole platform involved in structuring a transplant center with stool bank was established. The criteria for donor selection, processing and storage of samples, handling of recipients before and after the procedure, routes of administration, short and long-term follow-up of transplant patients were determined. Donor selection was conducted in three stages: pre-screening, clinical evaluation and laboratory screening. Most of the candidates were excluded in the first (75.4%) and second stage (72.7%). The main clinical exclusion criteria were: recent acute diarrhea, overweight (body mass index ≥25 kg/m2) and chronic gastrointestinal disorders. Four of the 134 candidates were selected after full screening, with a donor detection rate of 3%. CONCLUSION: The implantation of a transplant center, unprecedented in our country, allows the access of patients with recurrent or refractory C. difficile infection to innovative, safe treatment, with a high success rate and little available in Brazil. Proper selection of qualified donors is vital in the process of implementing a FMTC. The rigorous clinical evaluation of donors allowed the rational use of resources. A transplant center enables treatment on demand, on a larger scale, less personalized, with more security and traceability. This protocol provides subsidies for conducting FMT in emerging countries.

RESUMO CONTEXTO: O Transplante de microbiota fecal (TMF) é uma importante opção terapêutica para a infecção recorrente ou refratária pelo Clostridioides difficile, sendo método seguro e eficaz. Resultados iniciais sugerem que o TMF também desempenha papel relevante em outras afecções cuja patogênese envolve a alteração da microbiota intestinal. No entanto, seu uso sistematizado é pouco difundido, especialmente no Brasil. Na última década, surgiram múltiplos relatos e séries de casos utilizando diferentes protocolos para o TMF, sem padronização de métodos e com taxas de resposta variáveis. No Brasil, poucos casos isolados de TMF foram relatados sem a implantação de um Centro de Transplante de Microbiota Fecal (CTMF). OBJETIVO: O principal objetivo deste estudo foi descrever o processo de implantação de um CTMF com banco de fezes, em hospital universitário brasileiro, para tratamento de infecção recorrente e refratária pelo C. difficile. MÉTODOS: O CTMF foi estruturado dentro dos critérios exigidos e aprovados por organismos internacionais como o Food and Drug Administration, Grupo Europeu de Transplante de Microbiota Fecal e em consonância com os aspectos epidemiológicos e regulatórios nacionais. RESULTADOS: Foi estabelecida toda uma plataforma envolvida na estruturação de um centro de transplante com fezes congeladas. Determinou-se os critérios para seleção de doadores, processamento e armazenamento de amostras, manejo dos receptores antes e após o procedimento, uniformização de vias de administração do substrato fecal e seguimento a curto e longo prazo dos pacientes transplantados. A seleção dos doadores foi conduzida em três etapas: pré-triagem, avaliação clínica e exames laboratoriais. Boa parte dos candidatos foram excluídos na primeira (75,4%) e segunda etapa (72,7%). Os principais critérios clínicos de exclusão foram: diarreia aguda recente, excesso de peso (IMC ≥25 kg/m2) e distúrbios gastrointestinais crônicos. Quatro dos 134 candidatos foram selecionados após a triagem completa, com taxa de detecção de doadores de 3%. CONCLUSÃO: A implantação de um CTMF, inédito no nosso meio, possibilita o acesso de pacientes com infecção recorrente e refratária pelo C. difficile a tratamento inovador, seguro, com elevada taxa de sucesso e pouco disponível no Brasil. A seleção apropriada de doadores qualificados é vital no processo de implantação de um CTMF. A avaliação clínica rigorosa dos doadores permitiu o uso racional de recursos para realização de exames laboratoriais. Um CTMF possibilita tratamento sob demanda, em maior escala, menos personalizados, com mais segurança e rastreabilidade. Este protocolo fornece subsídios para a realização de TMF em países emergentes.

Transplantes de microbiota fecal para tratamento da colite pseudomembranosa (1958-2013): prioridade de descoberta e estilos de pensamento na literatura acadêmica / Fecal microbiota transplants in the treatment of pseudomembranous colitis (1958-2013): priority of discovery and thought styles in the academic literature

Resumo Em 1958, Eiseman e colaboradores publicaram o primeiro artigo científico relatando o uso de transplante de microbiota fecal para tratar casos graves de colite pseudomembranosa. A relevância desse trabalho inovador só foi reconhecida em 1990. A literatura acadêmica sobre o tema caracteriza-se por sucessivas reconstruções. Sugerimos que tais reconstruções foram orientadas por questões de atribuição de prioridade de descoberta científica nos termos propostos por Merton. A retomada do uso de transplantes de microbiota fecal é interpretada como processo de gênese de um fato científico, conforme Fleck: ocorre a mudança de um estilo de pensamento baseado no uso de antibióticos no tratamento de doenças infecciosas para outro que considera as relações ecológicas entre hospedeiros, vetores e agentes etiológicos de doenças.

Abstract In 1958, Eiseman and contributors published the first scientific paper reporting the use of fecal microbiota transplant for treating pseudomembranous colitis. The relevance of this innovative paper was only acknowledged in 1990. The academic literature on the theme is characterized by a narrative that has undergone successive revisions. We suggest that such revisions were based on claims of priority of scientific discoveries, as described by Merton. The revival of fecal microbiota transplants is interpreted as a process of genesis of a scientific fact, as defined by Fleck: there is a switch from a thought style based on the use of antibiotics to treat infectious diseases to another that accepts the ecological relations between hosts, vectors and parasites.

Trasplante de microbiota fecal: una revisión / Fecal Microbial Transplantation: A Review

Resumen La microbiota intestinal sana se define a partir de la presencia de grupos de microorganismos que potencian el metabolismo del huésped. Estos microorganismos le confieren resistencia ante las infecciones, así como ante procesos inflamatorios y frente al desarrollo de neoplasias o autoinmunidad. Además, favorecen las funciones endocrinas y colaboran con la función neurológica a través del eje intestino-cerebro. Por otro lado, el trasplante de microbiota fecal consiste en la introducción de una suspensión de materia fecal de un donante sano en el tracto gastrointestinal de otra persona, que generalmente es un paciente que presenta una patología concreta. Esto se realiza con el fin de manipular la composición de la microbiota del destinatario y contribuir al tratamiento de su problema. El concepto de trasplante de microbiota fecal rompe con la consideración tradicional de las bacterias como elementos dañinos y presta atención a las que, probablemente, son las más subvaloradas de las excretas del cuerpo humano: las heces. En efecto, se ha evidenciado su alta eficacia y el procedimiento es reconocido por el número de pacientes a los que ha ayudado, que se puede ya cifrar en miles. El objetivo de esta revisión de literatura fue describir aspectos básicos para comprender el trasplante de microbiota fecal enfocado al tratamiento de infecciones producidas por Clostridioides difficile.

Abstract Gut microbiota is defined as healthy when there are groups of microorganisms that enhance the host's metabolism, confer resistance to infections, inflammatory processes, the development of malignancies or autoimmunity, promote endocrine functions and support neurological function through the so-called gut-brain axis. Fecal microbial transplantation is the transfer of fecal matter from a healthy donor into the gastrointestinal tract of another person, usually a patient with a specific pathology, to manipulate the composition of the recipient's microbiota and contribute to the treatment of his or her condition. The concept of fecal microbial transplantation breaks with the traditional thought of bacteria as harmful elements and draws attention to what is probably the most undervalued of the human body's excreta: feces. Its high efficiency has been demonstrated and the procedure is recognized by the many patients it has helped, which can already be counted in thousands. The objective of this literature review was to describe the basics of fecal microbial transplantation for the treatment of Clostridioides difficile infections.

Chinese experts consensus on standardized methodology and clinical application of fecal microbiota transplantation / 中华胃肠外科杂志

Fecal microbiota transplantation (FMT) is to transplant the functional bacteria in the feces of healthy people into the patients' intestines, rebuild the new balance of intestinal flora, and achieve the treatment goals of intestinal and extraintestinal diseases. In the past 10 years, FMT has made a breakthrough in the treatment of intestinal and extraintestinal diseases, which is highly expected to treat difficult diseases. However, due to the complexity of FMT methodology and the lack of a unified standard, there is a high heterogeneity in FMT efficacy among various researches, greatly affected its clinical application. Under the initiative of Parenteral and Enteral Nutrition Branch of Chinese Medical Association, Enhanced Recovery after Surgery Branch of China International Health Care Promotion Exchange Association, China Microecological Treatment Innovation Alliance, and Microecology Committee of Shanghai Preventive Medicine Association, the first expert consensus on standardized methodology and clinical application of FMT was established in China, with a view to improving the efficacy of FMT, reducing the incidence of adverse reactions and promoting the clinical application of FMT.

Chinese experts consensus on clinical practice of the selection and establishment of fecal microbiota transplantation delivery routes / 中华胃肠外科杂志

Fecal microbiota transplantation (FMT) has gradually shown application prospects in the treatment of intestinal and extraintestinal diseases. In order to standardized FMT operation, based on the clinical experience of the Tenth People's Hospital Affiliated to Tongji University, combined with domestic and foreign literature, Parenteral and Enteral Nutrition Branch of Chinese Medical Association, Enhanced Recovery after Surgery Branch of China International Health Care Promotion Exchange Association, China Microecological Treatment Innovation Alliance, and Microecology Committee of Shanghai Preventive Medicine Association to formulated the" Chinese experts consensus on clinical practice of the selection and establishment of fecal microbiota transplantation delivery routes". It includes four parts: the selection of delivery route, the methodology of transplantation path establishment, the clinical application, and the monitoring of adverse events.